Molecular BIology of Cancer Topics
Angiogenesis is the formation of new blood vessels by extesions or branching of existing vessels. Many normal physiological processes require angiogenesis, amoung them: fetal development, tissue growth and repair (wound healing), and the female reproductive cycle. Regulation of angiogenesis is disrupted during cancer. Tumors cannot grow larger than about 1 mm in diameter without a blood supply. Hypoxia in a developing tumor will induce angiogenesis.
The processes of angiogenesis and tumor invasion are similar. In angiogenesis, vascular endothelial cells are separated from the stroma by a basement membrane, while tumor cells may or may not be sepaated from stroma by a basal membrane. In both processes, There is digestion of the basemnt membrane proteins by specific proteases in order to invade other areas. Both endothelial cells and tumor cells will then proliferate and migrate into the stroma, and specific proteases will digest the stroma to make way for new growth. But while vascular endothelial cells will differentiate to form blood vessels, tumor cells will not and thus continue proliferating and invading surrounding tissue.
A tumor's blood vesels aid in tumor growth by both perfusing the tumor and also secreting growth factors. Perfusion provides nutrients, oxygen and removal of catabolites. Growth factors from endothelial cels act in a paracrine fashion to support tumor growth. Such growth factors include FGFs, HB-EGF, G-CSF, PDGF and IGF-1. In fact, a higher blood vessel density in human breast tumors is associated with shorter survival times.
Angiogenic Switch
Angiogenesis has been observed as a discrete step in several animal cancer models, a step ofter referred to as the "angiogenic switch". This event occurs after hyperplasia (triggered by hypoxia) and just before the tumor becomes invasive.
Once the blood vessels have grown into a tumor, the tumor aquarires the capacity to metastazise to distant tissues. Tumor cells can invade blood vessels and thus gain access to the systemic circulation and travel in the bloodstream. After reaching other tissues through the blood stream, tumor cells can invade the new tissue by moving between endothelial cells into organ parenchyma.
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